Hypofractionated Stereotactic Radiosurgery in Treating Patients With Large Brain Metastasis

January 29, 2024 updated by: Bree Eaton, Emory University

Phase I Dose Escalation Trial of Hypofractionated Radiosurgery for Large Brain Metastasis

This phase I trial studies the side effects and best dose of hypofractionated radiosurgery in treating patients with large brain metastasis. Stereotactic radiosurgery can send x-rays directly to the tumor and cause less damage to normal tissue. Giving fractionated stereotactic radiosurgery may kill more tumor cells.

Study Overview

Detailed Description

PRIMARY OBJECTIVE:

To demonstrate the safety and feasibility of treating brain metastases or resection cavities greater than 3 cm with hypofractionated radiosurgery and to determine the maximum-tolerated radiation dose for hypofractionated radiosurgery (HR) delivered in 5 fractions, 2-3 fractions per week.

OUTLINE: This is a dose-escalation study.

Patients undergo hypofractionated stereotactic radiosurgery 2-3 times weekly (5 fractions total) for 2-3 weeks.

After completion of study treatment, patients are followed up at 1 month and then every 3 months thereafter.

Study Type

Interventional

Enrollment (Estimated)

25

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital/Winship Cancer Institute
      • Atlanta, Georgia, United States, 30342
        • Emory Saint Joseph's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Pathologic proven diagnosis of solid tumor malignancy
  • One brain metastasis or brain metastasis resection cavity with maximal diameter ≥ 3 cm (or ≥ 14 cc.) and ≤ 6 cm (or ≤ 113 cc.)
  • Recursive partitioning analysis (RPA) class I-II/ Karnofsky Performance status (KPS) ≥ 70%

Exclusion Criteria:

  • Prior stereotactic radiosurgery (SRS) to adjacent lesion such that planning target volume would have received more than 12 Gy
  • RPA class III (KPS < 70%)
  • Brain metastasis or resection cavity volume < 3 cm or > 6 cm
  • Radiosensitive or non-solid (eg. small cell lung carcinomas, germ cell tumors, leukemias, or lymphomas) or unknown tumor histologies
  • Concurrent chemotherapy (no chemotherapy starting 14 days before start of radiation)
  • Evidence of leptomeningeal disease by magnetic resonance imaging (MRI) and/or cerebrospinal fluid (CSF) cytology
  • Current pregnancy
  • More than 8 weeks between resection and radiosurgical procedure
  • Metastases to brain stem, midbrain, pons, or medulla or within 5 mm of the optic apparatus (optic nerves and chiasm)
  • Inability to undergo MRI evaluation for treatment planning and follow-up

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Hypofractionated Radiosurgery

HR (Hypofractionated Radiosurgery) delivered in 5 fractions, with a minimum of 2 and a maximum of 3 fractions being delivered per week, to patients with brain metastases or resection cavity greater than 3 cm and less than 6 cm.

Dose escalation will proceed according to the Escalation with Overdose Control (EWOC) method with a planned total enrollment of 24 patients, in 8 patient cohorts with 3 patients per cohort. A 4 month observation period will occur for each completed cohort prior to dose escalation, with a goal timeline for trial completion of 4 years from first patient enrollment.

Radiation Therapy will consist of partial brain irradiation delivered to the metastatic brain tumor or resection cavity, delivered in 5 treatments with 2-3 treatments delivered per week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum tolerated dose (MTD) of hypofractionated radiosurgery defined as the highest dose level where a grade 3 or greater with an attribution score of ≥ 3 develops in ≤ 2 of 6 patients in a dose group
Time Frame: 4 months
Graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. The rate of toxicities will be calculated with 95% confidence interval (CI).
4 months
Neurologic toxicity due to treatment, graded according to the CTCAE version 4.03
Time Frame: Up to 2 years
Calculated with 95% CI.
Up to 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Local control; lack of progression of disease in resection cavity as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria
Time Frame: 4 months
The median time to local brain progression will be calculated by Kaplan-Meier method with 95% CI.
4 months
Distant control: lack of progression of disease in surrounding brain as defined by RECIST criteria
Time Frame: 4 months
The median time to distant brain progression will be calculated by Kaplan-Meier method with 95% CI.
4 months
Freedom from failure/progression free survival
Time Frame: Up to 2 years
Up to 2 years
Overall survival (OS): death from any cause
Time Frame: Up to 2 years
The median of OS time with 95% CI will be calculated by Kaplan-Meier method.
Up to 2 years
Long-term neurocognitive outcomes: using the Hopkins Verbal Learning Test-Revised (HVLT-R), Mini Mental Status Exam (MMSE) and Cognitive Functioning Subscale of the Medical Outcomes Scale (MOS)
Time Frame: Up to 2 years
Neurocognitive effect will be regressed over time using generalized estimating equation (GEE) model. The population change over time (slope) will be estimated with 95% CI.
Up to 2 years
Quality of life (QOL) outcomes: using the quality of life questionnaire for the Functional Assessment of Cancer Therapy-Brain (FACT-Br).
Time Frame: Up to 2 years
QOL outcomes will be regressed over time using GEE model. The population change over time (slope) will be estimated with 95% CI.
Up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Bree Eaton, MD, Emory University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 24, 2012

Primary Completion (Actual)

April 11, 2023

Study Completion (Actual)

September 18, 2023

Study Registration Dates

First Submitted

October 10, 2012

First Submitted That Met QC Criteria

October 10, 2012

First Posted (Estimated)

October 12, 2012

Study Record Updates

Last Update Posted (Actual)

January 30, 2024

Last Update Submitted That Met QC Criteria

January 29, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • IRB00055063
  • P30CA138292 (U.S. NIH Grant/Contract)
  • NCI-2012-01933 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • RAD2156-11 (Other Identifier: Winship Cancer Institute)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Unspecified Adult Solid Tumor, Protocol Specific

Clinical Trials on Hypofractionated Radiosurgery

3
Subscribe